136 INTERNAL SECRETIONS OF THE OVARY 



ing hormone under the influence of the ovum itself. They 

 state (24) ' From a functional analysis of the follicle through 

 its various stages of growth, it seems probable that the produc- 

 tion of this hormone is referable ultimately to the metabolism 

 of the ovum itself as the dynamic centre of the follicle/ while 

 Hartman (271) in discussing the production of oestrus in the 

 opossum says, 'What element of the ovary constitutes the source 

 of stimuli that lead to procestrus and to cestrus? The 

 opossum affords an unequivocal answer which is in full accord 

 with the clear and succinct statements by both Allen and 

 Robinson, in which they make out a case for the Graafian 

 follicles. Their reasons I consider conclusive.' Robinson's (537) 

 work on the ferret led him to conclude that 'the phenomena of 

 procestrus and oestrus only appear when a group of follicles 

 has attained a stage of development which may be called 

 pre-inseminal maturity, and the phenomena are due to some 

 secretion produced by the follicles in that phase of their develop- 

 ment.' In a recent paper Zondek and Aschheim (650) conclude 

 that the oestrus-producing hormone is elaborated by the theca 

 interna of the follicle. These workers implanted into ovariecto- 

 mized mice various portions of the human ovary; only the theca 

 interna implants caused a positive reaction. Even very recently 

 Hammond and Marshall (267) have stated in connection with 

 the vaginal oestrous changes in the ferret, ' This outward sign 

 of the production of the oestrous hormone we consider is due to 

 the presence of ripe follicles in the ovaries since it is absent 

 during anoestrus, when only small follicles are present.' All 

 these statements, however, are made on the evidence of 

 functional correlation, and the whole hypothesis that the mature 

 follicle is responsible for the production of oestrus has resulted 

 from the elimination of other probabilities rather than from 

 experimental work. 



Time relation of follicular maturation and operation of the 

 oestrus-producing stimulus. Evidence that the maturing Graa- 

 fian follicle is not the causative factor in the production of 

 oestrus is forthcoming from the fact that the real maturation 

 of the follicle only begins after the oestrus-producing stimulus 

 has become active. It has been known for some time (425) that 

 double ovariectomy may be followed shortly afterwards by the 



